The PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment
PROFILE
1 other identifier
observational
1,600
1 country
1
Brief Summary
Prostate cancer is now the most common cancer in men in the Western world. In the United Kingdom (UK), there were over 52,000 new cases diagnosed in 2016-2018 and a lifetime risk of 1 in 8. Prostate cancer (PrCa) can run in some families and research studies have identified several genetic changes in Caucasian populations that are thought to increase the risk of developing prostate cancer. Other studies have shown that men from certain ethnic groups also have a higher risk of prostate cancer, and this includes men of black African or black African-Caribbean ancestry. This study aims to look at men with a higher risk of prostate cancer based on their ethnicity, family history and/or genetic predisposition to see whether any of these genetic changes are present in their DNA (genetic material) and whether this could be a helpful screening tool in prostate cancer screening programmes. It is thought that many genetic changes are involved in the development of prostate cancer and research is being carried out worldwide to identify these genetic changes. Some of these changes may cause a very slight increase in prostate cancer risk while others may cause a much larger increase in risk of developing prostate cancer. The investigators will invite (i) men of any ethnicity with a family history of prostate cancer; (ii) men of black African or black African-Caribbean ancestry; and (iii) men of any ethnicity with a known genetic predisposition to having prostate cancer (e.g., being known to have inherited a gene mutation that increases risk of prostate and/or being known to be in the top tenth percentile of the polygenic risk score (high PRS score prior to enrolment) for targeted prostate screening (Prostate Specific Antigen (PSA) testing, MRI and a biopsy of the prostate gland) and genetic profiling. The outcome of these prostate cancer screening investigations will be compared with the genetic profiles of those taking part in the study in order to look for certain genetic changes in the gene code that are thought to increase prostate cancer risk. This research will help us to determine what the role of such genetic profiling is in a prostate cancer screening programme and if it helps identify men at high prostate cancer risk.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Mar 2015
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 9, 2015
CompletedFirst Submitted
Initial submission to the registry
July 13, 2015
CompletedFirst Posted
Study publicly available on registry
September 7, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
July 25, 2025
July 1, 2025
11.8 years
July 13, 2015
July 24, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
The association of specific genetic profiles and biomarkers to predict outcome of prostate screening in men at higher genetic risk
To investigate the role of targeted prostate cancer screening in men at higher genetic risk (i.e. family history, ethnicity, gene mutation status), its association with specific genetic profiles and biomarkers as predictive tools of the risk of developing prostate cancer and to correlate these with genetic risk.
5 years
Secondary Outcomes (5)
The incidence and aggressiveness of prostate cancer in men at higher genetic risk.
5 years
The association of Diffusion Weighted MRI (DW-MRI) findings with prostate biopsy results.
5 years
The incidence of abnormal imaging (using 3D ultrasound combined with shear wave elastography) and correlation with biopsy outcome and to correlate standard 12 core prostate biopsies with targeted biopsies based on abnormalities identified at DWMRI.
5 years
The association of biological sample biomarker profiles with prostate biopsy result.
5 years
The association of quantitative imaging biomarkers with prostate biopsy result
5 years
Study Arms (3)
Family History Cohort
Men of any ethnicity with a family history of prostate cancer defined as: * Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at \<70 years * Men with two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at \<70 years * Men with three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age
Black African / Black African-Caribbean Cohort
Men of black African or black African-Caribbean ancestry defined as: Both parents and all 4 grandparents being of black African or black African-Caribbean ancestry.
High-risk gene mutation cohort
Men of any ethnicity with a genetic predisposition to having prostate cancer e.g., being known to have inherited a gene mutation that increases risk of prostate cancer (gene mutation including BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in the study protocol); and/or being known to have a high polygenic risk score (PRS) (defined as being in the top tenth percentile prior to enrolment).
Interventions
All men will be offered a MRI and prostate biopsy and they can either opt to undergo these procedures at baseline irrespective of PSA level at baseline or they can undergo PSA-only screening until clinically indicated based on an age-defined PSA threshold, at which point, they will undergo prostate MRI and biopsy once their PSA reaches the threshold.
Eligibility Criteria
350 men in each cohort\* \*The family history cohort will overrecruit to a total of 800, until 350 participants undergo MRI \& biopsy; both the Black and high-risk gene cohorts will overrecruit to a total of 400 participants each, to replace any participants who withdrew and/or any protocol non-compliant cases (e.g. those who underwent MRI but did not complete the biopsy).
You may qualify if:
- Either:
- Men of any ethnicity with a positive family history of PrCa defined as:
- Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at \<70 years
- Men with two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at \<70 years
- Men with three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age
- Men of black African or black African-Caribbean ancestry defined as:
- Both parents and all 4 grandparents being of either black African or black African-Caribbean ancestry.
- Men of any ethnicity with a genetic predisposition to having prostate cancer e.g., being known to have inherited a gene mutation that increases risk of prostate cancer (e.g. BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in the study protocol); and/or being known to have a high polygenic risk score (PRS) (defined as being in the top tenth percentile prior to enrolment).
- Age 40- 69 years
- WHO performance status 0-2
- Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow up schedule.
You may not qualify if:
- Previous cancer with a life expectancy of less than five years.
- Previous PrCa
- Negative biopsy within one year before recruitment
- Co-morbidities making prostate biopsy risk unacceptable (anticoagulants or antiplatelet medication including Warfarin, Clopidogrel, Apixaban, Dabigatran or other NOAC (Novel Oral Anti-Coagulant); poorly controlled diabetes, cardiovascular/respiratory disease, immunosuppressive medication or splenectomy)
- Men with body mass index (BMI) 40 and above.
- Men with BMI 35 and above plus other co-morbidities.
- Contraindications to having an MRI (non-MRI compliant pacemakers, aneurysm clips, metallic cardiac valve/stent, Ventriculo-Peritoneal (VP) shunt, cochlear implant, neurotransmitter, metallic foreign bodies in eye(s), other metalwork, claustrophobia)
- Any significant psychological conditions that may be worsened or exacerbated by participation in the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Institute of Cancer Research, United Kingdomlead
- Royal Marsden NHS Foundation Trustcollaborator
- University of Cambridgecollaborator
- University of Oxfordcollaborator
- Queen Mary University of Londoncollaborator
Study Sites (1)
Institute of Cancer Research and Royal Marsden Hospital
Sutton, Surrey, SM2 5PT, United Kingdom
Related Links
Biospecimen
Serum, plasma, urine, DNA, RNA
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rosalind A Eeles
Institute of Cancer Research, United Kingdom
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 13, 2015
First Posted
September 7, 2015
Study Start
March 9, 2015
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
July 25, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
Anonymised data can be applied for via the Data Access Committee